| Bioactivity | FG-2216 (IOX3) is a potent and orally active inhibitor of HIF prolyl hydroxylase-2 (PHD2), with an IC50 of 3.9 μM. FG-2216 induces robust erythropoietin and modest fetal hemoglobin in vivo[1][2][3]. | ||||||||||||
| Target | IC50: 3.9 nM (PHD2) | ||||||||||||
| Invitro | FG-2216 (50-100 μM; 24 h) stimulates erythropoietin (Epo) secretion by PHD2 inhibition in Hep3B cells[1].FG-2216 (3-100 μM; 24 h) stabilizes HIF-1α and HIF-2α in Hep3B cells[1]. | ||||||||||||
| In Vivo | FG-2216 (40-60 mg/kg; p.o. twice a week for 150 d) induces erythropoiesis and a small elevation of hemoglobin (HbF) expression, and is well tolerated in rhesus macaques[2].FG-2216 (50 mg/kg; p.o. once daily for 4 or 12 d) increases hematocrit, red blood cell counts, and hemoglobin levels in mice[1].FG-2216 (40-60 mg/kg; a single p.o) reversibly induces endogenous Epo in rhesus macaques[2]. Animal Model: | ||||||||||||
| Name | FG-2216 | ||||||||||||
| CAS | 223387-75-5 | ||||||||||||
| Formula | C12H9ClN2O4 | ||||||||||||
| Molar Mass | 280.66 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Hong YR, et al. [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin secretagogues. Bioorg Med Chem Lett. 2013 Nov 1;23(21):5953-7. [2]. Hsieh MM, et al. HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques. Blood. 2007 Sep 15;110(6):2140-7. [3]. Bernhardt WM, et, al. Inhibition of prolyl hydroxylases increases erythropoietin production in ESRD. J Am Soc Nephrol. 2010 Dec;21(12):2151-6. |